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NCT07489495PHASE3Recruiting

A Clinical Study of Belzutifan (MK-6482) and Zanzalintinib in People With Renal Cell Carcinoma (RCC) (LITESPARK-034/LS-034/MK-6482-034)

Merck Sharp & Dohme LLC

Start Date

4/9/2026

Completion Date

11/27/2030

Summary

Researchers are looking for new ways to treat advanced renal cell carcinoma (RCC). A standard (usual) treatment for certain people with RCC is belzutifan (a study medicine), which is a targeted therapy. Targeted therapy is a treatment that works to control how specific types of cancer cells grow and spread. Researchers want to learn if adding another targeted therapy called zanzalintinib (another study medicine) can treat more people with advanced RCC than belzutifan alone. The goal of this study is to learn if people who receive belzutifan and zanzalintinib live longer overall and without the cancer getting worse compared to people who receive belzutifan and placebo.

Eligibility Criteria

Age Range: 18 years to No maximum

Inclusion Criteria: The main inclusion criteria include but are not limited to the following: * Has a histologically confirmed diagnosis of unresectable, advanced renal cell carcinoma (RCC) with clear cell component (with or without sarcomatoid features) ie, Stage IV RCC per American Joint Committee on Cancer (8th Edition) * Has measurable disease per Response Evaluation Criteria In Solid Tumors Version 1.1 (RECIST 1.1) * Has received no more than 3 prior systemic regimens for RCC, including only 1 prior anti-Programmed Cell Death-1/Programmed Cell Death 1 Ligand 1 therapy Exclusion Criteria: For exclusion criteria: The main exclusion criteria include but are not limited to the following: * Has any of the following: a pulse oximeter reading \<92% at rest, requires intermittent supplemental oxygen, or required chronic supplemental oxygen * Has clinically significant cardiovascular disease within 12 months from first dose of study intervention * Has deep vein thrombosis within 3 months before randomization unless stable, asymptomatic, and treated with therapeutic anticoagulation for at least 4 weeks before randomization * Has a left ventricular ejection fraction ≤50% or below the institutional (or local laboratory) normal range as determined by multigated acquisition or echocardiogram * Has had major surgery within 8 weeks before randomization * Has current pneumonitis/interstitial lung disease * Has a history of human immunodeficiency virus infection * Has Hepatitis B or Hepatitis C virus infection * Has a known additional malignancy that is progressing or has required active treatment within the past 3 years * Has a history of solid organ transplant * Has not adequately recovered from major surgery or has ongoing surgical complications

Interventions

DRUG

Belzutifan

DRUG

Zanzalintinib

DRUG

Placebo

Interested in This Trial?

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Conditions

Carcinoma, Renal Cell

Locations

Northwest Georgia Oncology Centers, a Service of Wellstar Cobb Hospital ( Site 0102)

Marietta, Georgia 30060

United States

The West Clinic, P.C. ( Site 0115)

Germantown, Tennessee 38138

United States

Centro Oncologico Korben ( Site 0254)

CABA, Buenos Aires C1426AHB

Argentina

Hospital Italiano de Buenos Aires ( Site 0253)

Ciudad de Buenos Aires, Buenos Aires 1181

Argentina

Instituto de Investigaciones Clinicas Mar del Plata ( Site 0250)

Mar del Plata, Buenos Aires B7600FZO

Argentina

Centro Privado de RMI Río Cuarto S.A. II ( Site 0255)

Río Cuarto, Córdoba Province X5800ALB

Argentina

Sanatorio Parque ( Site 0251)

Rosario, Santa Fe Province S2000DSV

Argentina

Instituto de Oncología de Rosario ( Site 0257)

Rosario, Santa Fe Province S2000KZE

Argentina

Instituto Alexander Fleming ( Site 0252)

CABA, C1426ANZ

Argentina

Centro Oncológico Riojano Integral ( Site 0256)

La Rioja, X5004BAL

Argentina

COE (Centro Oncológico de Excelencia) ( Site 0259)

San Juan, J5402BGA

Argentina

Macquarie University ( Site 2700)

Macquarie University, New South Wales 2109

Australia

CEDOES ( Site 0303)

Vitória, Espírito Santo 29055-450

Brazil

Instituto do Câncer e Transplante de Curitiba ( Site 0300)

Curitiba, Paraná 80510-130

Brazil

Liga Norte Riograndense Contra o Câncer ( Site 0307)

Natal, Rio Grande do Norte 59062-000

Brazil

Fundação Faculdade Regional de Medicina de São José do Rio Preto ( Site 0302)

São José do Rio Preto, São Paulo 15090-000

Brazil

Masarykuv onkologicky ustav ( Site 0903)

Brno, Brno-mesto 656 53

Czechia

Fakultni nemocnice Ostrava ( Site 0904)

Ostrava, Ostrava Mesto 708 52

Czechia

Fakultni nemocnice Hradec Kralove ( Site 0902)

Hradec Králové, 500 05

Czechia

Fakultni nemocnice v Motole ( Site 0900)

Prague, 150 06

Czechia

Herlev Hospital ( Site 1002)

Herlev, Capital Region 2730

Denmark

Aarhus Universitetshospital, Skejby ( Site 1001)

Aarhus, Central Jutland 8200

Denmark

Centre Antoine Lacassagne ( Site 1209)

Nice, Alpes-Maritimes 06189

France

Hopital Europeen Marseille ( Site 1216)

Marseille, Bouches-du-Rhone 13003

France

LBM ONCOPOLE CLAUDIUS REGAUD ( Site 1215)

Toulouse, Haute-Garonne 31059

France

CHU Angers ( Site 1204)

Angers, Maine-et-Loire 49933

France

Clinique Victor Hugo Le Mans-Oncology-Radiotherapy ( Site 1203)

Le Mans, Pays de la Loire Region 72000

France

CHU de Saint-Etienne ( Site 1202)

Saint Priest En Jarez, Pays de la Loire Region 42271

France

Universitätsklinikum Jena ( Site 1313)

Jena, Thuringia 07747

Germany

Alexandra General Hospital of Athens ( Site 1400)

Athens, Attica 115 28

Greece

ATTIKON GENERAL UNIVERSITY HOSPITAL ( Site 1401)

Athens, Attica 124 62

Greece

Metropolitan Hospital ( Site 1402)

Athens, Attica 185 47

Greece

Rambam Health Care Campus ( Site 1600)

Haifa, 3109601

Israel

Meir Medical Center. ( Site 1603)

Kfar Saba, 4428164

Israel

Rabin Medical Center ( Site 1602)

Petah Tikva, 4941492

Israel

Sheba Medical Center ( Site 1601)

Ramat Gan, 5265601

Israel

IRCCS - Istituto Romagnolo per lo Studio dei Tumori (IRST) "Dino Amadori" ( Site 1809)

Meldola, Emilia-Romagna 47014

Italy

Azienda Ospedaliera Universitaria Careggi ( Site 1807)

Florence, Tuscany 50134

Italy

Fondazione IRCCS Istituto Nazionale dei Tumori ( Site 1800)

Milan, 20133

Italy

AO Santa Maria della Misericordia ( Site 1805)

Perugia, 06132

Italy

Istituto Nazionale Tumori Regina Elena ( Site 1804)

Roma, 00144

Italy

Fondazione Policlinico Universitario Agostino Gemelli IRCCS - Università Cattolica del Sacro Cuore ( Site 1801)

Roma, 00168

Italy

Maastricht UMC+ ( Site 1901)

Maastricht, Limburg 6229 HX

Netherlands

Nederlands Kanker Instituut Antoni van Leeuwenhoek (NKI AVL) ( Site 1900)

Amsterdam, North Holland 1066 CX

Netherlands

Haga Ziekenhuis locatie Leyweg ( Site 1906)

The Hague, South Holland 2545 AA

Netherlands

AIDPORT Sp. z o.o. ( Site 2118)

Skórzewo, Greater Poland Voivodeship 60-185

Poland

Pratia MCM Krakow ( Site 2115)

Krakow, Lesser Poland Voivodeship 30-727

Poland

Mazowiecki Szpital Wojewódzki w Siedlcach-Siedleckie Centrum Onkologii ( Site 2102)

Siedlce, Masovian Voivodeship 08-110

Poland

MTZ Clinical Research Powered by Pratia ( Site 2107)

Warsaw, Masovian Voivodeship 02-172

Poland

Narodowy Instytut Onkologii - Oddzial w Gliwicach ( Site 2106)

Gliwice, Silesian Voivodeship 44-102

Poland

Severance Hospital, Yonsei University Health System ( Site 2903)

Seoul, 03722

South Korea

Asan Medical Center ( Site 2901)

Seoul, 05505

South Korea

Samsung Medical Center ( Site 2902)

Seoul, 06351

South Korea

Hospital Universitario Virgen del Rocio ( Site 2306)

Seville, Andalusia 41013

Spain

Institut Català d'Oncologia - L'Hospitalet ( Site 2305)

L'Hospitalet de Llobregat, Barcelona 08908

Spain

HOSPITAL GENERAL UNIVERSITARIO GREGORIO MARAÑON ( Site 2301)

Madrid, Madrid, Comunidad de 28007

Spain

Hospital Universitari Vall d'Hebron ( Site 2303)

Barcelona, 08035

Spain

Hospital Insular de Gran Canaria ( Site 2308)

Las Palmas, 35016

Spain

Hospital Universitario 12 de Octubre ( Site 2300)

Madrid, 28041

Spain

Fundación Instituto Valenciano de Oncología ( Site 2307)

Valencia, 46009

Spain

Hacettepe Universite Hastaneleri ( Site 2500)

Sıhhiye, Ankara 06230

Turkey (Türkiye)

Adana Medical Park Seyhan Hastanesi ( Site 2505)

Adana, 01140

Turkey (Türkiye)

Ankara University Health Practice and Research Hospitals ( Site 2506)

Ankara, 06620

Turkey (Türkiye)

Trakya University Medical Faculty Hospital ( Site 2502)

Edirne, 22030

Turkey (Türkiye)

Koc Universitesi Hastanesi ( Site 2501)

Istanbul, 34010

Turkey (Türkiye)

The Christie Hospital NHS Foundation Trust ( Site 2601)

Withington, Manchester M20 4BX

United Kingdom